title: Muscle injury, vimentin expression, and nonsteroidal anti-inflammatory drugs predispose to cryptic group A streptococcal necrotizing infection.
abstract: BACKGROUND
  Myonecrosis due to group A streptococci (GAS) often develops at sites of nonpenetrating muscle injury, and nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the severity of these cryptic infections. We have previously shown that GAS bind to vimentin on injured skeletal muscles in vitro. The present study investigated whether vimentin up-regulation in injured muscles in vivo is associated with homing of circulating GAS to the injured site and whether NSAIDs facilitate this process.
  
  
  METHODS
  M type 3 GAS were delivered intravenously 48 h after eccentric contraction (EC)-induced injury of murine hind-limb muscles. Vimentin gene expression and homing of GAS were followed by real-time reverse-transcriptase polymerase chain reaction and quantitative bacteriology of muscle homogenates, respectively. In separate experiments, ketorolac tromethamine (Toradol) was given 1 h before GAS infusion.
  
  
  RESULTS
  Vimentin was up-regulated approximately 8-fold 48 h after EC. Significantly more GAS were found in moderately injured muscles than in noninjured controls. NSAIDs greatly augmented the number of GAS in injured muscles.
  
  
  CONCLUSIONS
  Vimentin may tether circulating GAS to injured muscle, and NSAIDs enhance this process. Strategies targeting the vimentin-GAS interaction may prevent or attenuate GAS myonecrosis. Use of NSAIDs should increase suspicion of cryptic GAS infection in patients with increasing pain at sites of nonpenetrating muscle injury.
authors.affiliation: Infectious Diseases Section, Veterans Affairs Medical Center, 500 W. Fort Street, Boise, ID 83702, USA.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Hamilton
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Bayer
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Stevens
authors.forename: Richard L
authors.initials: RL
authors.lastname: Lieber
authors.forename: Amy E
authors.initials: AE
authors.lastname: Bryant
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D005260:Female; D005786:Gene Expression Regulation; D051379:Mice; D018482:Muscle, Skeletal / Q000473:pathology; D009135:Muscular Diseases / Q000382:microbiology* / Q000473:pathology; D012307:Risk Factors; D013290:Streptococcal Infections / Q000382:microbiology*; D013297:Streptococcus pyogenes / Q000502:physiology*; D014746:Vimentin / Q000235:genetics / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D014746:Vimentin